Portola Pharmaceuticals (Nasdaq:PTLA) today announced that
enrollment has begun in a Phase 3 study to evaluate the safety and
efficacy of andexanet alfa, the Company's investigational
recombinant Factor Xa inhibitor reversal agent, with Bayer
HealthCare and Janssen Pharmaceuticals Inc.'s Factor Xa inhibitor
XARELTO® (rivaroxaban). Portola is developing andexanet alfa, an
FDA-designated breakthrough therapy, as a potential first-in-class
agent to reverse the anticoagulation activity of Factor Xa
inhibitor-treated patients who are experiencing a major bleeding
episode or who require emergency surgery.
"This Phase 3 study with XARELTO® is the second
registration-enabling study that we have initiated this year under
an Accelerated Approval pathway to achieve our goal of bringing
andexanet alfa, an FDA-designated breakthrough therapy, to market
as quickly as possible. As the number of patients taking novel oral
anticoagulants has increased, so has the number of hospital visits
by patients who need an antidote," said John T. Curnutte, M.D.,
Ph.D., executive vice president, research and development at
Portola.
Phase 3 Study Design
The randomized, double-blind, placebo-controlled Phase 3 study
is designed to evaluate the efficacy of andexanet alfa (initial IV
bolus followed by continuous infusion) in rapidly reversing
XARELTO-induced anticoagulation. The study will evaluate the
efficacy of andexanet alfa in healthy volunteers (ages 50-75 years)
as demonstrated by biomarker endpoints, including anti-Factor Xa
levels, plasma free fraction of the anticoagulant and thrombin
generation. In the first part of the study, approximately 40
healthy volunteers will be given XARELTO® 20 mg once daily and then
randomized in a 2:1 ratio to andexanet alfa administered as an 800
mg IV bolus or to placebo. In the second part of the study,
approximately 40 healthy volunteers will be randomized in a 2:1
ratio to andexanet alfa administered as an IV bolus followed by a
continuous infusion for 120 minutes or to placebo. Study
participants will be followed for up to 43 days to assess
safety.
About the Need for a Factor Xa Inhibitor Reversal
Agent
Currently, millions of patients are treated with XARELTO® and
other Factor Xa inhibitors for short-term use or chronic
conditions, and the anticoagulant market is expected to continue to
grow with the adoption of novel oral anticoagulants. Clinical trial
results suggest that, annually, between 1-4 percent of patients
treated with Factor Xa inhibitors will experience major bleeding,
and an additional 1 percent will require emergency surgery.
Currently, standard clinical measures are employed to manage these
events. Development of an agent specifically designed to reverse
the activity of Factor Xa inhibitors may provide an important
treatment option for patients who experience a major bleeding event
or require emergency surgery. About Andexanet Alfa
Andexanet alfa is a first-in-class recombinant, modified Factor Xa
molecule being developed as a direct reversal agent for patients
receiving a Factor Xa inhibitor who suffer a major bleeding episode
or who may require emergency surgery. Andexanet alfa acts as a
Factor Xa decoy that targets and sequesters with high specificity
both direct and indirect Factor Xa inhibitors in the blood. Once
bound, the Factor Xa inhibitors are unable to bind to and inhibit
native Factor Xa, thus allowing for the restoration of normal
hemostatic processes.
About the Andexanet Alfa Clinical Development
Program Portola is evaluating andexanet alfa in Phase 3
studies with Bristol-Myers Squibb Company (BMS) and Pfizer Inc.'s
Eliquis® (apixaban) and Bayer HealthCare and Janssen's XARELTO®
(rivaroxaban). The randomized, double-blind, placebo-controlled
studies are designed to evaluate the safety and efficacy of
andexanet alfa in reversing Eliquis or XARELTO® induced
anticoagulation rapidly after an IV bolus and sustaining that
effect through a continuous infusion.
Earlier this year, Portola entered into Phase 3 collaboration
agreements with BMS/Pfizer and Bayer HealthCare/Janssen that
included upfront payments and additional potential milestone
payments to cover the costs of the clinical development program
with Eliquis and XARELTO®, respectively. Portola retains 100
percent worldwide commercialization rights to andexanet alfa.
Results from two Phase 2 proof-of concept studies demonstrated
that andexanet alfa immediately reversed the anti-Factor Xa
activity of Eliquis and XARELTO® in healthy volunteers. Andexanet
alfa provided temporary reversal through the administration of an
IV bolus infusion or sustained reversal with the addition of an
extended infusion. In clinical practice, some patients may require
short-acting reversal of their anticoagulant, while others, such as
those who need emergency surgery, may require long-acting reversal.
Andexanet alfa has the potential to address numerous clinical
scenarios by allowing for flexible and controlled reversal.
Andexanet alfa has been shown to be well tolerated in clinical
studies, which have included more than 90 volunteers, with no
thrombotic events or antibodies to Factor Xa or Factor X
observed.
Data from a Phase 2 proof-of-concept study evaluating andexanet
alfa as a reversal agent for enoxaparin, a low molecular weight
heparin, will be presented at the 60th Scientific and
Standardization Committee meeting of the International Society on
Thrombosis and Haemostasis (ISTH) in June. A Phase 2
proof-of-concept study with Daiichi Sankyo's edoxaban is ongoing,
and a Phase 2 proof-of-concept study with Portola's Factor Xa
inhibitor betrixaban is planned.
About Portola Pharmaceuticals, Inc. Portola
Pharmaceuticals is a biopharmaceutical company developing product
candidates that have the potential to represent significant
advances in the fields of thrombosis and other hematologic
diseases. The Company is advancing its three wholly-owned programs
using novel biomarker and genetic approaches that may increase the
likelihood of clinical, regulatory and commercial success of its
first-in-class therapies. Portola's partnered program is focused on
developing selective Syk inhibitors for inflammatory
conditions.
Betrixaban Portola's wholly-owned, oral, once-daily Factor Xa
inhibitor betrixaban is being evaluated in the only biomarker-based
Phase 3 study for hospital-to-home prophylaxis of venous
thromboembolism (VTE) in acute medically ill patients. Betrixaban's
distinct properties may have the potential to allow the agent to
demonstrate efficacy without the significant increase in the rate
of major bleeding that was seen in this patient population with
other Factor Xa inhibitors. If approved, betrixaban could be the
first anticoagulant for both hospital and post-discharge VTE
prophylaxis and the standard of care in this large market of more
than 30 million patients worldwide.
Andexanet Alfa
Portola's second product candidate in the area of thrombosis,
andexanet alfa, has the potential to be a first-in-class reversal
agent to reverse the effects of Factor Xa inhibitors in patients
who suffer a major bleeding episode or who require emergency
surgery. Portola has entered into clinical collaboration agreements
with all of the manufacturers of direct Factor Xa inhibitors --
Bristol-Myers Squibb and Pfizer (Eliquis® [apixaban]), Bayer
HealthCare and Janssen Pharmaceuticals (XARELTO® [rivaroxaban]),
and Daiichi Sankyo (edoxaban) -- while retaining all commercial
rights to andexanet alfa. Andexanet alfa has been designated as a
Breakthrough Therapy by the U.S. Food and Drug Administration.
Cerdulatinib* (PRT2070)
Portola's product candidate in the area of hematologic cancer,
cerdulatinib, is an orally available molecule that uniquely
inhibits two validated tumor proliferation pathways -- spleen
tyrosine kinase (Syk) and janus kinase (JAK). It is currently being
evaluated in a Phase 1 study in patients with leukemias or
lymphomas with a focus on genetically-defined subtypes, as well as
in patients who have failed therapy due to relapse or acquired
mutations. For more information, visit www.portola.com and follow
the Company on Twitter @Portola_Pharma.
Forward-looking statement
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, statements regarding:
Portola's plans for future clinical studies and pursuit of an
Accelerated Approval process for andexanet alfa, anticipated growth
in the market for anticoagulants, clinical trial cost, design and
timing, and the potential efficacy, safety and activity of
andexanet alfa, betrixaban and cerdulatinib. Risks that contribute
to the uncertain nature of the forward-looking statements include:
the accuracy of Portola's estimates regarding its ability to
initiate and/or complete its clinical trials; the success of
Portola's clinical trials and the demonstrated efficacy of
Portola's product candidates thereunder; the accuracy of Portola's
estimates regarding its expenses and capital requirements; our
ability to manufacture andexanet alfa; regulatory developments in
the United States and foreign countries; Portola's ability to
obtain and maintain intellectual property protection for its
product candidates; and the loss of key scientific or management
personnel. These and other risks and uncertainties are described
more fully in our most recent filings with the Securities and
Exchange Commission, including our Annual Report on Form 10-K and
our Quarterly Report on Form 10-Q for the first quarter of 2014,
which we expect to file on or about May 12, 2014. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. Portola undertakes no
obligation to update such statements to reflect events that occur
or circumstances that exist after the date on which they were
made.
*Cerdulatinib is a proposed International Nonproprietary Name
(pINN).
CONTACT: Investor Contact:
Alexandra Santos
Portola Pharmaceuticals
ir@portola.com
650.246.7239
Media Contact:
Joey Fleury
BrewLife
jfleury@brewlife.com
415.946.1090
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